Newswise — Cancer treatment typically involves surgery, radiation therapy, chemotherapy, hormone therapy or biological therapy. An oncologist may use one therapy or a combination of methods, depending on the type and location of the cancer, whether the disease has spread, the patient’s age and general health, and other factors.

This is the third in a series of three reports focusing on cancer research at Georgia Tech. The first highlighted efforts to understand how cancer arises, and the second featured cancer detection and diagnostic techniques.

ATTACKING CANCER STEM CELLS
Recent evidence suggests that certain cancers may persist or recur after treatment because a few cells – called cancer stem cells – survive existing therapy and then seed new tumors. These stem cells can be particularly resistant to chemotherapy and radiation.

“In the future, effective cancer therapy may require the detection and elimination of cancer stem cells in tumors,” said Gang Bao, the Robert A. Milton Chair in Biomedical Engineering in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University. “Developing a method to detect cancer stem cells is challenging because evidence suggests there is only one cancer stem cell for every 100,000 to 1 million cancer cells in tumor tissue, so the method must be very sensitive.”

Bao and postdoctoral fellow Won Jong Rhee recently developed a new method that effectively discriminates cancer stem cells from other cancer cells by locating protein markers on the surface of stem cells and stem cell-specific genes inside cancer stem cells. The work was published on April 2, 2009, in the journal BMC Biotechnology.

The researchers located live stem cells by simultaneously detecting the presence of the stem cell surface protein marker SSEA-1 with dye-labeled antibodies and stem cell-specific mRNA – called Oct-4 – inside the stem cells using molecular beacons.

“By fluorescently imaging the level of Oct-4 mRNA in the cytoplasm of live stem cells with molecular beacons, we were able to increase the detection sensitivity and specificity,” explained Bao, who is also a Georgia Tech College of Engineering Distinguished Professor.

Since initially developing this method for detecting and isolating stem cells, the research team has been improving the method’s efficiency and specificity by targeting multiple mRNAs and cell surface markers using molecular beacons and antibodies.

According to Bao, the next stage for this research is to isolate cancer stem cells from human tumor tissue samples.

“After we isolate the cancer stem cells, we still need to learn more about them, including the pathways or genes responsible for their development and whether they behave the same when isolated from different patients. Then we need to identify drug molecules that can kill them,” he added.

Funding for this research is provided by the Emory-Georgia Tech National Cancer Institute Center for Cancer Nanotechnology Excellence (CCNE). This work was funded by grant number U54CA119338 from the National Institutes of Health (NIH). The content is solely the responsibility of the principal investigator and does not necessarily represent the official view of the NIH.

IMPROVING RADIATION THERAPY
One critical challenge in radiation therapy has always been how best to minimize damage to normal tissue while delivering therapeutic doses to cancer cells. Intensity-modulated radiation therapy (IMRT) is an advanced type of radiation treatment that utilizes computer-controlled linear accelerators to deliver precise radiation doses to tumors while avoiding critical organs. Clinicians can use IMRT to treat difficult-to-reach tumors – such as tumors in the brain, head, neck, prostate, lung and liver – with new levels of accuracy.

“Constructing an IMRT treatment plan that radiates the cancerous tumor without impacting adjacent normal structures is challenging,” explained Shabbir Ahmed, an associate professor in the Stewart School of Industrial and Systems Engineering at Georgia Tech. “Because of the many possible beam geometries and the range of intensities, there are an infinite number of treatment plans and many metrics to assess their quality.”

To develop better treatment plans faster, Ahmed began working with School of Industrial and Systems Engineering professor Martin Savelsbergh and graduate student Halil Ozan Gozbasi, as well as collaborators Ian Crocker, Timothy Fox and Eduard Schreibmann from the Emory University School of Medicine’s Department of Radiation Oncology. Funding for this research
was provided by Emory University.

The Georgia Tech researchers built on an existing model and developed a fully automated program that simultaneously generates several high-quality treatment plans satisfying the clinician-provided requirements. The optimization program uses three-dimensional computed tomography images of the patient and information about (1) the type, location and size of the tumor; (2) maximum allowable doses to non-cancerous organs; and (3) the patient’s health.

“Previous models would produce one treatment plan in an hour and then if it was not exactly what the clinician wanted, someone would have to change the requirements and rerun the program to create a new treatment plan,” explained Ahmed. “Our program produces several optimized solutions in a fraction of the time.”

The technology, which has been tested successfully on real brain, head/neck and prostate cancer cases, produces clinically acceptable treatment plans in less than 15 minutes.

INCLUDING MOTION AND BIOLOGICAL INFORMATION IN TREATMENT PLANNING
Intensity-modulated radiation therapy (IMRT) treatment planning is challenging because some organs, such as the prostate, move due to normal daily volume changes in the bladder and rectum. In addition, a tumor can change shape during radiation treatment, which typically lasts five days a week for five to 10 weeks.

By collecting computed tomography images over time, the researchers can track every spatial point of interest in the tumor and surrounding area during each phase of the breathing cycle. This allows them to develop treatment plans that account for breathing, motion and shape changes throughout the treatment regimen.

“Accounting for motion in the image-guided treatment planning dramatically improves under-dosing the tumor tissue and even reduces the dose to normal tissue and critical organs,” noted Lee, who is also director of the Center for Operations Research in Medicine and HealthCare at Georgia Tech.

In lung cancer cases, that means reducing the average dose of radiation to the normal lung tissue, heart and esophagus. For liver cancer, the researchers have reduced the radiation delivered to normal liver and non-liver tissues.

In another project, Lee and Marco Zaider, an attending physicist and head of brachytherapy physics in medical physics at Memorial Sloan-Kettering Cancer Center in New York, are incorporating biological information into treatment planning for prostate cancer IMRT and brachytherapy – the placement of radioactive “seeds” inside a tumor.

Using magnetic resonance spectroscopy, the researchers identified regions of the prostate that had denser populations of tumor cells. These areas could then be targeted with an escalated radiation dose, while maintaining a minimal dose to critical and normal tissues.

“One of our main concerns is avoiding normal tissue toxicity, so by targeting only the ‘bad’ pockets of tumor cells, we hope to improve the outcome,” said Zaider. “Biological optimization attempts to target tissue that is potentially responsible for metastatic spread.”

Lee’s research has been supported by the National Science Foundation (NSF), the National Institutes of Health (NIH) and the Whitaker Foundation.

This project was partially supported by Award No. 0800057 from the NSF and Award No. 5UL1RR025008-02 from the NIH. The content is solely the responsibility of the principal investigator and does not necessarily represent the official views of the NSF or NIH.

ASSESSING A TUMOR’S ABILITY TO CREATE NEW BLOOD VESSELS
Cancer manifests itself in different ways – some cancers proceed slowly, while others spread aggressively. These differences have led clinicians to believe that personalized cancer therapies might be the best solution for treating the disease.

Now, new research, published in the June 2009 issue of the journal PLoS ONE, is providing insight into the aggressiveness of tumors. This information could facilitate development of a personalized treatment regimen.

Because aggressive tumors create more new blood vessels to sustain their growth, researchers designed long-circulating nanoprobes that were 100 nanometers in diameter and contained a contrast agent that could only seep into tumors from blood vessels that were growing and therefore leaky.

“We exploited the fact that the nanoprobes are too big to leak out of normal blood vessels, but they can leak out of newly forming tumor vessels because these immature vessels have bigger holes in them,” explained lead author Ravi Bellamkonda, a professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University.

The study showed that the degree of “leakiness” of tumor blood vessels to the nanoprobe correlates to its expression of vascular endothelial growth factor (VEGF), a protein that stimulates the growth of new blood vessels in tumors.

“Clinical studies have shown that VEGF expression varies among tumors, with higher levels of VEGF expression correlating with unfavorable prognosis, but scientists haven’t been able to non-invasively determine VEGF expression levels in individual tumors until now,” said Bellamkonda, who is also a Georgia Cancer Coalition Distinguished Scholar.

After injecting the contrast-containing nanoprobes into rats with six-day-old breast cancer tumors, the research team visualized the levels of nanoprobe accumulation in the tumor using digital mammography. The results showed increased “leakiness,” nanoprobe accumulation and tumor growth rates in tumors with higher levels of VEGF. Similar-size tumors showed various degrees of angiogenesis and blood vessel permeability, which caused them to behave differently, emphasizing the inherent variability in tumors and the need for a personalized approach to each tumor.

“In the future, instead of just measuring the size of a tumor, clinicians can quantify the leakiness of tumor blood vessels to determine the extent of angiogenesis in each tumor and decide which patients should undergo anti-angiogenic therapy or other aggressive treatment regimens,” added Bellamkonda.

Collaborators on this research include Efstathios Karathanasis, formerly a Coulter Department postdoctoral fellow and currently an assistant professor in the Department of Biomedical Engineering at Case Western Reserve University; Carl D’Orsi and Ioannis Sechopoulos of the Department of Radiology and Winship Cancer Institute at the Emory University School of Medicine; and Ananth Annapragada, an associate professor of health information sciences at the University of Texas, Houston.

This project is supported by the National Science Foundation (NSF) (Award Nos. 0401627 and ERC-EEC-9731643), the Nora Reed Foundation, the Wallace H. Coulter Foundation and the Georgia Cancer Coalition. The content is solely the responsibility of the principal investigator and does not necessarily represent the official view of the NSF.

DEVELOPING A NEW APPROACH TO TARGETED CANCER THERAPY
A new therapeutic strategy for cancer treatment is to inhibit enzymes called histone deacetylases, which play an important role in the regulation of gene expression. Vorinostat (SAHA) – a histone deacetylase inhibitor – was approved by the U.S. Food and Drug Administration in 2006 to treat an immune system cancer called cutaneous T-cell lymphoma.

While these inhibitors are clinically valuable, they typically inhibit many of the 18 different histone deacetylase subtypes, a process that can be harmful to essential cell functions throughout the body.

“Our goal is to create inhibitors for these enzymes that target specific cancerous organs so that we can exploit their anti-cancer activity in the cancerous tissue areas only and not negatively affect other areas of the body,” said Adegboyega “Yomi” K. Oyelere, who holds the Blanchard Assistant Professorship in the Georgia Tech School of Chemistry and Biochemistry.

In the January 22, 2009, issue of the Journal of Medicinal Chemistry, Oyelere and Georgia Tech biology assistant professor Yuhong Fan described a new class of potent non-peptide histone deacetylase inhibitors that can be selectively accumulated in the lungs.

To create them, the researchers modified the amine sugar portion of common antibiotics such as azithromycin and clarithromycin with a histone deacetylase inhibiting structure. Experiments have shown that the new compounds are more potent than SAHA and are lung-specific. As a result of these preliminary findings, Oyelere was recently awarded a five-year, $1.5 million grant from the National Institutes of Health to continue this lung cancer research.

Oyelere is also designing histone deacetylase inhibitors that can be taken up by the hormones expressed on the surface of hormone-positive breast cancer cells to stop the cells from dividing. For this project, he is working with Donald Doyle, an associate professor in the Georgia Tech School of Chemistry and Biochemistry.

“A majority of hormone-positive breast cancers develop resistance to anti-cancer hormone drugs, so if we can exploit the ability of our compounds to be accepted by hormone-positive breast cancers, whether they’re resistant or not, this could lead to the identification of new, broad anti-cancer agents for targeted cancer therapy,” explained Oyelere.

Next up on Oyelere’s list of cancers to tackle with this approach is prostate cancer.

This work is funded by grant number R01CA131217 from the National Institutes of Health (NIH). The content is solely the responsibility of the principal investigator and does not necessarily represent the official view of the NIH.

As an assistant professor in the Georgia Tech School of Chemical and Biomolecular Engineering, Taite is developing cancer drug delivery vehicles composed of a gold nanoshell core with dendrimers attached to the surface. Dendrimers are polymers that exhibit a tree-like structure with many branches and cavities where chemotherapy drugs can be encapsulated.

The dendrimers are synthesized with targeting molecules on their surfaces that can seek out and bind to cancer cells. Introduced into the body, they bind to cancer cells, and when near-infrared light shines on the body, the gold nanoshell heats up. That heat leads the dendrimers to shrink, the drug to be released, and the tumor cells are exposed to both the heat and drug therapies.

“In some cases, ablation takes place at temperatures that can be uncomfortable to the patient, so we are trying to develop dendrimers that require lower transition temperatures to release the drug,” said Taite. “We believe that even if the lower temperature does not kill all of the cancer cells, it will still damage them enough that they will become extremely vulnerable to the drug, ultimately still leading to cell death.”

Amanda Lowery, a research fellow in radiation oncology at Vanderbilt University, is collaborating with Taite on this research.

Taite is also designing another delivery vehicle to carry and release nitric oxide for the treatment of aggressive brain tumors. She is focusing on nitric oxide because it has the ability to cross the blood-brain barrier and help other molecules cross both the blood-brain barrier and the blood-tumor barrier.

“Nitric oxide has been shown to increase the sensitivity of certain tumors to chemotherapeutics and radiation, so we are working to form materials that can be attached to imaging particles and a chemotherapeutic that can be targeted to specific tumors. That would significantly enhance current tumor treatment approaches,” explained Taite.

The targeted nitric oxide delivery system will be used to study the efficacy of using nitric oxide to sensitize brain tumors to treatment and improve patient prognosis.

“My ultimate goal in designing all of these drug delivery systems is to improve patient quality of life and reduce cancer recurrence,” added Taite.

ENABLING PERSONALIZED DRUG DELIVERY
The search is on for drug delivery systems that allow treatment to be tailored to an individual patient and a particular tumor. Researchers at Georgia Tech are contributing to the pursuit by developing ways to program the assembly and disassembly of multi-particle drug delivery vehicles.

“Cancer is a complicated disease, and we wanted to find a way that we could simultaneously deliver many different particles to the tumor site as a package and, upon arrival, break open the packages so that the individual particles could then carry out their particular functions,” said Valeria Milam, an assistant professor in the Georgia Tech School of Materials Science and Engineering.

Individuals benefit from this type of personalized treatment through the increase in the drug’s cancer-killing power and the reduction of its toxic side effects. Milam and her students are using short nucleic acid polymers called oligonucleotides to connect the particle surfaces for simultaneous delivery of different therapeutic and diagnostic agents to the tumor site.

“To assemble the pieces, we are using short oligonucleotides as the glue because they have a weak, yet sufficient affinity for their partner strand,” explained Milam, who is also a Georgia Cancer Coalition Distinguished Cancer Scholar. “This allows us to direct particles A and B to attach to particle C through oligonucleotide linkages, while keeping particles A and B unconnected to one another.”

Then, to disassemble the particle package, a competitive oligonucleotide – one with a stronger affinity as a partner strand – is introduced into the system. These competitive strands displace the original partner strands, allowing the package to break open. Milam and her team are further improving the drug delivery vehicle so that it can be initially camouflaged to avoid any host response that would clear it out of the body before arriving at the tumor site.

“Our ongoing work involves initially masking the presence of the therapeutic carriers by applying a stealth coating to the vehicle surface,” noted Milam. “Then, after the desired circulation time, the coating will be shed to reveal cancer-targeting ligands.”

While Milam’s experiments are still at the laboratory stage, her ultimate goal is to develop materials that can be used in the clinical setting to treat cancer. Former Georgia Tech students Christopher Tison and Sonya Parpart, and current graduate students James Hardin and Bryan Baker, also worked on this research. This work is currently supported by the Georgia Cancer Coalition, a National Science Foundation CAREER award, and the U.S. Army. It was previously supported by the Emory-Georgia Tech National Cancer Institute Center for Cancer Nanotechnology Excellence (CCNE).

This material is based upon work supported by the U.S. Army (Award No. W911NF-09-1-0479), National Institutes of Health (NIH) (Award No. U54CA119338) and National Science Foundation (NSF) (Award No. DMR-0847436). Any opinions, finding, conclusions or recommendations expressed are those of the principal investigator and do not necessarily reflect the views of the U.S. Army, NIH or NSF.

ANALYZING GENE EXPRESSION DATA TO PREDICT DRUG RESPONSE
The major clinical goals in applying gene expression profiling to cancer are to develop predictors of drug response that will guide more individualized therapies.

Ming Yuan, an associate professor in the Stewart School of Industrial and Systems Engineering at Georgia Tech, is using computational and mathematical approaches to analyze how gene expression evolves over time in individuals with breast cancer and whether these patterns can predict treatment outcome. Specifically, Yuan is studying how gene expression evolves during the menstrual cycle and whether there is any association between these patterns and cancer relapse.

“Our goal is to weed out the genes that just change expression level due to a woman’s menstrual cycle and not because of tumor progression or treatment,” explained Yuan, who is also a Georgia Cancer Coalition Distinguished Cancer Scholar. “We want to know which genes are abnormally expressed over time and behave differently than the majority of genes because that would make them likely drug targets.”

Better predictors of relapse risk could help cancer patients make better treatment decisions in consultation with their physicians. Yuan is working with William Hrushesky of the University of South Carolina and the Dorn Veterans Affairs Medical Center on this research.

In another project, Yuan is collaborating with two University of Wisconsin professors, Alan Attie and Christina Kendziorski, to conduct expression quantitative trait loci (eQTL) studies. This analysis allows the researchers to identify genomic hot spots that regulate gene transcription and expression on a genome-wide scale.

“We want to determine which regions of the genome are most predictive of expression variations, but it’s challenging because there are a vast range of possible regulatory loci and many of them are correlated, making it hard to differentiate which is actually responsible for a given effect,” said Yuan.

Yuan’s analysis will determine the hot spots as well as how those genes are connected to each other, but ultimately, the proposed genes will need to be studied further by biologists.

Yuan’s research is supported by the National Science Foundation and the Georgia Cancer Coalition.

ScienceDaily (June 3, 2010) — A minimally invasive technique used to destroy kidney tumors with an electrically controlled heating probe showed similar effectiveness as surgical removal of tumors in curbing cancer recurrence rates for up to five years after treatment.

In an article available online in the journal Cancer, Dr. Jeffrey Cadeddu, professor of urology and radiology at UT Southwestern Medical Center, reported the outcomes of more than 200 patients who were treated with radiofrequency ablation (RFA).

Once the diagnosis of tumor is confirmed and the RFA technique is agreed upon, a needle-like probe is placed inside the tumor. The radiofrequency electricity waves passing through the probe heat up tumor tissue and destroy it. Surgeons view the RFA procedure with the aid of imaging devices such as computed tomography (CT scan).

Of the 208 patients who underwent the RFA procedure, 160 were diagnosed with renal cell carcinoma, a type of kidney cancer that is slow-growing but malignant and able to spread easily to other organs. Those patients had three- and five-year survival rates of more than 95 percent.

"These types of cancers aren't typically fast-growing, but there are between 40,000 and 50,000 cases of kidney cancers diagnosed each year in the United States," Dr. Cadeddu said. "The fact that cancer survival rates were comparable to surgical interventions is very encouraging."

Currently, many patients who are diagnosed with primary tumors that originate inside the kidney are treated surgically.

"The standard treatment is usually a partial nephrectomy, where the surgeon removes the tumor and some surrounding tissue via open or laparascopic surgery," said Dr. Cadeddu. "With surgery, there is a 5 percent to 10 percent risk of bleeding and an associated need for transfusion, as well as an increased chance of readmission for the patient. Of course, the recovery time is longer as well."

With open surgery, surgeons go in through a patient's abdomen or flank to remove the kidney tumor. A laparascopic partial nephrectomy involves doctors accessing the organ through several small incisions in a patient's abdomen. The recovery time for open surgery is about six to eight weeks and three to four weeks for laparascopic procedures.

With RFA, 90 percent of the patients are able to go home the same day, said Dr. Cadeddu, but the real advantage to RFA is its superior preservation of kidney tissue.

"Preserving kidney function has been clearly demonstrated to maximize quality of life and length of life for patients with kidney tumors," Dr. Cadeddu said. "Whenever possible, we try to save as much of the kidney as we can."

It's been 40 years since President Richard Nixon signed the National Cancer Act. NCI has spent $100 billion on understanding cancer biology since then - the equivalent of $10, or two designer cups of coffee, per U.S. resident per year - and billions more have been spent developing new drugs and treatments to work against those biological processes.

Still, cancer kills more than 566,000 people worldwide each year, the equivalent of three 747s crashing every single day.

Today, serious people argue that our whole strategy in solving the cancer problem might be wrong, that too much effort has gone into understanding cancer and not enough into simply applying what we already know. Cancer scientists like myself have even heard claims that we're ignoring solutions to the cancer problem-that we're sitting on "the cure for cancer."

The truth isn't pretty: Cancer death rates are declining, yet improvement in cancer mortality has lagged behind other killers like cardiovascular disease. Only about 5 percent of new cancer drugs that are tested in people get approved for clinical use, compared with about 20 percent of cardiovascular drugs. This number doesn't count the number of drugs that fail before they are tested in people.

Although we've made much progress, we don't even fully understand how the most fundamental decisions in cell biology occur, such as how cells decide to die or grow.

Here's one reason why we need more - much more - understanding of cancer biology. We are taking on the most powerful force in biology: Darwinian natural selection.

A tumor is a population of many types of cells that are all trying to grow and survive. When we treat cancer, we are trying to kill the tumor cells (or stop their growth) by applying strong selective (or evolutionary) pressure. And, cancer cells evolve to avoid selection we applied-the "fittest" cancer cells survive.

Cells that grow back after treatment probably found a way to avoid that treatment. We see this in the clinic: When tumors come back, they usually don't respond to the drugs that worked before.

This problem of Darwinian selection pressure doesn't really apply to other major diseases in which cells die because they are damaged-think heart or neurodegenerative disease.

The best hope we have of making a big impact on the number of people who survive cancer is to understand even more about how the biology works. For example, by understanding how cell growth and survival are controlled, we might predict how tumor cells will undergo natural selection to avoid a drug's effects and be able to design a strategy to stop cells from beating the treatment.

We have some examples of this already. We know that tumors that use a growth pathway called EGFR can be stopped for a while using an EGFR inhibitor drug. Eventually, the cells find another pathway to use to grow. We've figured out that these EGFR-positive tumors use a bypass mechanism driven by a cell receptor called Met.

By understanding how the cells use Met to grow when their preferred EGFR growth pathway is blocked, we've learned we can combine EGFR and Met inhibitors to kill more cancer cells than using either agent alone.

However, for most cancer drugs, we don't know what pathways cancer cells might activate to get around a drug-induced roadblock. Until we do, we will probably continue to throw away potentially useful treatments. Indeed, I suspect that some of those 95 percent of failed cancer drugs would have been useful if only we knew more about how they worked.

We need more research into cancer biology, because without really understanding what is going on, our efforts to apply that research will be doomed to failure. Understanding cancer biology isn't just the best way forward; it is the only way forward, if we really want to solve the cancer problem.

ScienceDaily (June 7, 2010) — Scripps Research Institute scientists have discovered a new way to target and destroy a type of cancerous cell. The findings may lead to the development of new therapies to treat lymphomas, leukemias, and related cancers.

The study, which appears in the June 10, 2010 edition of the journal Blood, showed in animal models the new technique was successful in drastically reducing B cell lymphoma, a cancer of immune molecules called B cells.

"[The method] worked immediately," said Scripps Research Professor James Paulson, who led the research. "We are very interested in moving this technology forward to see if it would be applicable to treatment of humans and to investigate other applications for this kind of targeting."

A Sweet Spot

In his research program at Scripps Research, Paulson has studied glycoproteins, which are proteins decorated with sugars, for many years. While these molecules have traditionally proven challenging to understand, limiting their pharmaceutical applications, Paulson has pioneered new techniques to study and manipulate these enigmatic molecules.

In the new research, Paulson and his colleagues applied some of the lab's insights to a problem with great medical relevance -- finding a new way to target and destroy cancer cells.

Specifically, in the new study the team set out to attack B cell lymphoma (which includes Hodgkin lymphoma and non-Hodgkin lymphoma), a type of cancer diagnosed most frequently in older individuals and those with compromised immune systems. Each year approximately 70,000 people are diagnosed with B cell lymphomas in the United States alone, according to the American Cancer Society. While the drug rituximab is often effective at treating the disease, each year 22,000 patients still die from B cell malignancies.

Normally, B cells provide an important immune function circulating throughout the bloodstream to help in the attack of infectious agents. But when B cells become cancerous, the question becomes how to pick them out of the crowd of other molecules in the body to target them for destruction, ideally without affecting surrounding tissues.

Because of his previous research, Paulson knew that B cells had a unique receptor protein on their surfaces that recognized certain sugars found on glycoproteins. Could the team create a viable potential therapeutic that carried these same sugars to identify and target these cells?

Toward a "Magic Bullet"

Paulson and colleagues decided to try a unique approach to this problem.

The scientists combined two different types of molecules into one, using both new and tried-and-true technology. One part of the potential therapeutic was composed of a specialized sugar (ligand) recognized by the B cell receptor, called CD22, expressed on the surface of B cells. This was attached to the surface of the other portion of the potential therapeutic, a nanoparticle called a "liposome," loaded with a potent dose of a proven chemotherapy drug.

"The advantage is that we already know a lot about how liposomes act in the body because they are approved drugs," said Paulson. "They have a long circulatory half-life. They are formulated so they are not taken up by the macrophages in the liver. So we just used the same formulation, attached these ligands, and went right into in vivo studies."

The chemotherapy drug chosen was doxorubicin, which is used in the treatment of a wide range of cancers. First identified in the 1950s, doxorubicin was originally isolated from bacteria found in soil samples taken from a 13th-century Italian castle. The team used a nanoparticle formulation of doxorubicin called Doxil, in which the drug is encapsulated inside the liposomal nanoparticle, which Paulson explains protects normal cells from the drug until it reaches the cancer.

Normally Doxil is passively delivered to tumors by exiting leaky tumor vasculature, and the drug slowly leaks out to kill the tumor. But by decorating the nanoparticles with the CD22 ligand, the team made the nanoparticles into a type of Trojan horse that is actively targeted to and taken up by human lymphoma B cells, carrying the drug inside the cell.

In the current research, the team administered their new compound to immune-compromised mice that had been infected with B cell lymphoma cells (Daudi Burkitt type). The team used two different formulations of the molecule, one decorated with two percent ligands, the other with five percent. The mice received only one dose.

The results were remarkable. No mouse in the control group lived to the end of the 100-day trial, but five of the eight mice receiving the higher ligand dose of the compound survived.

The scientists then looked to see if they could detect any residual tumor cells in the survivors, knowing that in a mouse that is paralyzed by the disease 95 percent of the cells in the bone marrow are tumor cells.

"When we looked at the bone marrow of those that had survived to 100 days, we couldn't detect any [tumor cells]," said Paulson. "Our detection limit was down to 0.3 percent. It was pretty impressive."

To extend the results, the scientists examined their compound's activity in blood samples from human patients with three types of B cell lymphomas -- hairy cell leukemia, marginal zone lymphoma, and chronic lymphocytic leukemia. The scientists found that the compound also effectively bound to and destroyed these diseased B cells.

Encouraged by the results, the team is now working to further improve the drug platform, looking for ways to increase the specificity of B cell targeting as well as exploring the technology's use with other chemotherapy agents.

The research was funded by grants from the National Institute of Allergy and Infectious Diseases (NIAID) and the National Institute of General Medical Sciences (NIGMS) of the National Institutes of Health (NIH).

Why does cancer seem so profound to us when compared to other diseases? And why do some patients clam up about their illness, while others are compelled to bear witness?

I’ve been asking myself these questions a lot lately. It will be two years next month since I had my prostate surgically removed, then learned that I unexpectedly had an aggressive Stage 3 cancer. In turn, that led to 33 radiation sessions and six months of hormone therapy.

I haven’t had any treatment in well over a year and my blood tests are right where I want them to be. Yet, I still feel haunted by cancer, can’t quite shake the depression and fatigue that arrived with the disease. They squat on my shoulders like two old crows.

Cancer does capture our imaginations. A quick check on Amazon.com shows about 44,000 books with the word “cancer” in the title (including a certain racy novel by Henry Miller), but only about 8,000 with “heart disease” on the cover, and a mere 311 holding forth on poison ivy.

One aspect of the bleak and profound chord that cancer strikes within us is the shame and silence that sometimes accompany the disease. My friend Gary, who was treated for prostate cancer last year, said that when he was a kid family members used to say that someone “went to Europe,” rather than admit that person had been killed by cancer.

My old and ornery New Hampshire relatives thought they could whup cancer through denial and sheer Yankee cussedness — no matter where they were bleeding from or how much. In the end, they died of their shame in raging silence.

I understand them, partly. A cancer diagnosis in their day was generally a death sentence — and people don’t want to talk about their executioners. Then there was the guilt, caused by thinking that maybe they were somehow at fault for being sick. And cancer’s earthiness, often striking at sexual organs and waste functions, also hushed them.

But in their fear, my relatives deified cancer, calling it “the Cancer,” the capital “C” understood. Sometimes, our entire culture deifies cancer. President Richard M. Nixon declared war on cancer in 1971, and John Wayne, in his best swaggering voice, once boasted that he had “licked the big “C.” (Mr. Wayne was wrong, however.)

For me, cancer’s profundity is about the biological betrayal at the cellular level, that somehow a killer has grown inside us. When I ponder cancer, I imagine darkness creeping into my body from some unknown abyss. And there’s that awful sense of being devoured, cell by cell.

We know that we’ve been damaged by our cancers and, too, by the treatment — by the radiation and the chemo and the scalpels. It reminds me of classic Orwellian double-speak from the Vietnam War: “We had to destroy the patient to save him, sir!”

And there’s always the nagging feeling that we could end up starring in an unwanted sequel to our cancer movie: The alien hordes from inner space have been vanquished, for now.

Ultimately, we’re offered a choice in the cultural exile cancer cultivates. We can just shrug and become one of the mute living dead, or we can try to become free-range sages, sharing our tales and trying to bring a little light into this world.

That’s why more than 400 people -– patients, caregivers and perhaps a few cancer-patient groupies -– gathered at a Relay for Life cancer fundraiser in Montclair, N.J., last Friday night. We were there to share tears and stories; there to hug each other and smile; there to remind ourselves that, damn it, we were not our cancers.

As we walked throughout the hot and muggy night till daybreak, our very movement defied the stillness that cancer tries to insist on.

"Further down the line we could create a drug that would bring COMMD1 protein levels back to normal, or even above normal, in the tumor to hopefully affect cancer cell invasion," said Dr. Ezra Burstein, assistant professor of internal medicine and molecular biology and senior author of the study appearing in the June issue of the Journal of Clinical Investigation. "If the cancer cells have already started invading other organs, maybe further invasion would be halted or even regressed."

Dr. Burstein is a member of a research team that years ago discovered the COMMD family of proteins and its abilities. They discovered that one of those proteins, COMMD1, inhibits NF-kB, a key factor that activates genes involved in inflammation and that is often involved in helping cancer cells survive. COMMD1 also regulates a protein called HIF, which plays a role in the survival of cells in areas of low oxygen, a common feature of cancer. For example, enhanced HIF activity is associated with tumor growth, metastasis and poor clinical outcomes for cancer patients.

Because COMMD1 has this dual role in regulating both NF-kB and HIF, the researchers thought that COMMD1 might be inactivated or repressed in tumors. This study supports their hypothesis, as the scientists found decreased amounts of this protein in a variety of human cancers and the decreased expression of COMMD1 also was associated with more invasive cancers.

COMMD1 suppression in cancer cells leads to enhanced activity of both NF-kB and HIF, a one-two punch that makes the cancer more invasive, Dr. Burstein said.

In a review of 63 patients with endometrial cancer, the researchers determined that those whose tumors had the lowest levels of COMMD1 had the worst clinical outcomes.

Using mice, it was also discovered that the COMMD1-deficient cells were more invasive when implanted. The researchers then generated mouse melanoma cells that produced an overabundance of COMMD1, and injected those cells back into healthy mice. The number of metastatic lung tumors that resulted was greatly reduced when the cells expressed greater levels of COMMD1.

"This is the first study that clearly links COMMD1 to human disease and substantiates what we would've expected based on the prior work we have done on this protein," he said. "COMMD1 is yet another player in the very important and complicated cancer invasion process."

The next step, Dr. Burstein said, will be to investigate what changes in the tumor environment may be responsible for reducing levels of COMMD1 in cancer cells.

Dr. Xicheng Mao, instructor in internal medicine at UT Southwestern, was a co-first author. Researchers at the University of Michigan Medical School, at University Medical Center Utrecht, University Medical Center Groningen, and Maastricht University Medical Centre in the Netherlands also participated in the study.

ScienceDaily (May 20, 2008) — Immune cells called macrophages can destroy tumor cells by producing inflammatory proteins that are toxic to the tumor. But the environment inside the tumor somehow halts this production and instead causes the cells to make proteins that promote tumor growth.

The new study identifies a protein, called IKK(beta), that drives this pro-tumor switch. This protein normally stimulates protective inflammation.

But in the context of tumors, the study shows, IKK(beta) also blocked the activity of a protein that turns on anti-tumor genes.

When the scientists inactivated IKK(beta) in macrophages from mouse tumors, the tumor-friendly cells went on the attack. These cells also secreted proteins that attracted professional tumor-killing cells that helped to shrink the tumors.

The researchers are now conducting clinical trials to determine whether macrophages from cancer patients can be similarly reprogrammed into tumor killers.

ScienceDaily (June 9, 2010) — To diagnose cancer reliably, doctors usually conduct a biopsy including tissue analysis, which is a time-consuming process. A microscopic image sensor, fitted in an endoscope, is being developed for in vivo cancer diagnosis, to speed up the detection of tumors.

Early detection is the key to the successful treatment of cancer. But not every lump turns out to be a malignant tumor. To find out whether cancerous cells are present, doctors usually conduct a biopsy and examine the removed tissue under the microscope. This process is not only very stressful for the patient but also highly time consuming. Research scientists at the Fraunhofer Institute for Photonic Microsystems IPMS in Dresden are aiming to considerably speed up cancer diagnosis. They have developed a microscope head with a diameter of just eight millimeters which can optically resolve and magnify tissue cells measuring just 10 to 20 micrometers. Fitted in the tip of an endoscope it will be used for in vivo cancer diagnosis, inserted in the body as in a minimally invasive surgical operation. The scientists envision that the MEMS (micro-electro-mechanical system) microscope head will eliminate the need for biopsies. Diagnosis in real time would enable doctors to decide on the necessary course of treatment more quickly.

"Microscopic image recorders that can be used on endoscopes have not been available up to now. We have developed the first laser-based sensor for this purpose," says Dr. Michael Scholles, business unit manager at the IPMS. "In classic endoscopy using macroscopic imaging, the job can be done by CCD or CMOS image sensors, as used in digital cameras and cellphones. For endomicroscopy, however, MEMS-based image sensors are highly advantageous because they can magnify even the smallest object fields, such as cells, without the need for a large lens. We have combined the sensor with a microscanner mirror to achieve the required resolution of 10 micrometers and can therefore massively magnify the tiniest structures."

But how does the system function? The laser itself is located in the operating theater. The laser light is conducted via a transmitting fiber to the microscanner mirror fitted in the tip of the endoscope. This deflects the laser beam and illuminates the suspicious tissue specifically. A glass-fiber bundle in the tip of the endoscope transmits the reflected light to the external sensor, which thus receives a signal containing the image information. A detector precisely measures the position of the scanner mirror, indicating which area of the scene is being illuminated at the specific point in time. A two-dimensional image can thus be completely reconstructed by combining the position and image sensor signals.

"An important aspect of the development was to produce a suitable microassembly for the endoscope head. Here we faced the challenge of making the complete system suitable for installation in the endoscope, and we managed to do it. In future our microscope head will be produced in large quantities in an automated process for subsequent installation in endoscopes," explains Scholles. The expert envisages a wide range of applications for the system: "It could be used not only in medical and biological microscopy but also in technical endoscopy, for instance to examine cavities in buildings or to inspect the insides of engines and turbines." The microscope head has already been produced as a demonstrator and can be seen at the Optatec trade show in Frankfurt from June 15 to 18 (Hall 3, Stand D50).

CHICAGO — Doctors reported gains against nearly every form of cancer at a conference that ended this week. Yet when Will Thomas heard about an advance against prostate cancer, he wanted to know just one thing: "Is it a cure?"

"I see billions and billions done on research, and it's all for treatment," said the Alabama man who has several friends with the disease. "When will they cure it?"

Many people share his frustration. The top achievements reported at the American Society of Clinical Oncology added an average of just two to six months of life. One pricey drug made headlines merely for delaying the time until ovarian cancer got worse.

Progress has always been slow for cancer treatment. New therapies are tested on people who are so sick and out of options that any extension of life is considered a success. A cure is not usually possible.

But some of the victories reported this week against breast and prostate cancer, leukemia and the deadly skin cancer called melanoma may be larger than they appear. These trends offer reason for optimism:

_ Newer drugs seem to be making a bigger difference for small, specific groups of patients, as companies develop treatments that more precisely target genes behind subtypes of cancer.

Pfizer Inc. rushed into late-stage testing one such drug: crizotinib, which is aimed at only 4 percent of lung cancer patients. More than 90 percent of them responded to the drug in initial tests. High response rates also have been reported for other novel drugs for melanoma and breast cancer driven by certain genes.

The hope: Develop enough of these specialized treatments that eventually every cancer patient will have something that works.

_ Quicker answers from smaller, focused studies. Pfizer's test of crizotinib will need only 318 patients and will be finished early next year. It also will test the drug earlier in the course of illness rather than as a last-ditch option.

"You don't really need big trials if it works so well," and the group of patients who stand to benefit can be identified in advance, said Dr. Roy Herbst, lung cancer chief at the University of Texas M.D. Anderson Cancer Center in Houston.

_ Big gains from novel combinations. All 66 patients testing a drug combo for the blood disease multiple myeloma saw a reduction in the amount of cancer they had by at least half. A 100 percent response rate is unheard of for any cancer and would not have occurred if two drugmakers had not teamed up to test their treatments together instead of against each other, said Dr. Paul Richardson of Boston's Dana-Farber Cancer Institute, who led the research.

The combo of Takeda Pharmaceutical Co.'s Velcade, Celgene Corp.'s Revlimid and the chemotherapy mainstay dexamethasone allowed more than half of patients to delay and perhaps avoid a bone marrow transplant — a harsh and risky treatment for the disease.

_ Comparison tests of long-used treatments. For decades, men with cancer that has spread beyond the prostate have been given hormone treatments with or without radiation, yet only a few studies have tested these against each other or together. A Canadian study found that combo treatment extended survival an average of six months in high-risk cases, and the oncology society said it could become a new standard of care.

"We're asking questions that should have been answered decades ago," said Dr. Len Lichtenfeld, the American Cancer Society's deputy chief medical officer.

_ Building on success. Since it was approved in 2003, the Novartis drug Gleevec has been the closest thing to a cure for any cancer. It has transformed chronic myeloid leukemia from a nearly-always fatal disease to one now manageable with a daily pill.

Yet a second-generation drug from Novartis — Tasigna — and Bristol-Myers Squibb Co.'s Sprycel did even better than Gleevec as initial treatment for those who are newly diagnosed, studies found. Sprycel and Tasigna are used now only when people fail on Gleevec.

_ New drugs from surprising sources. Eisai Inc.'s eribulin, derived from a sea sponge, improved survival for women with advanced breast cancer and could fill some key treatment gaps.

It comes "at a time when many of us thought there weren't new chemotherapy drugs being developed," because of all the focus on gene-targeting drugs, said Dr. Eric Winer, breast cancer chief at Dana-Farber. "This may be one of the last ones."

_ More hope that drugs for other conditions also can fight cancer. The Novartis bone-building drug Zometa improved survival for people with multiple myeloma in one study. Earlier research suggested it may help against breast cancer, and results of a definitive test of this are eagerly awaited.

_ Gentler treatments. More of the drugs being developed today are pills rather than infusions. Shorter, more focused radiation treatments are showing promise. Women need to have fewer lymph nodes removed to check for breast cancer. And new drugs have eased the nausea and vomiting that have made many cancer patients fear chemotherapy.

One issue is not improving: cost.

Personalized medicine will advance cancer care, said Dr. John Mendelsohn, president of the M.D. Anderson Cancer Center and head of a recent government panel on cancer research. But it will not be cheap, he said.

News from this week's gathering of the American Society of Clinical Oncology in Chicago, the world's largest annual cancer meeting, underscores how good we have become at turning new scientific principles into superior medicines. For those who gripe that progress from our huge investments in cancer research is too little or too slow, stunning results from two experimental drugs tell a different story.

Bristol Myers's drug Ipilimumab, the first treatment to extend the lives of patients with advanced melanoma skin cancer, is based on science that is 30 years in the making. Pfizer's drug Crizotinib, which shrank some of the most resistant and fatal forms of lung cancer, was developed as a result of science done over the last decade.

Developing drugs will always be a lengthy, iterative process. Ipilimumab's origins are a prime example. The drug springs from a modern understanding of how our immunity works that was first developed in academic labs in the 1980s. Private industry used this knowledge to make copies of antibodies—immune molecules that our bodies produce to fight disease—and turn them into medicines.

The first antibody drugs, developed in the mid 1980s, were made from mice. Human bodies quickly recognized these drugs as foreign particles and rapidly attacked them. This rendered the medicines ineffective or, worse, toxic.

A biotech company didn't develop the first really effective antibody drug, ReoPro for the treatment of heart attacks, until 1995. But it was just a fragment of an antibody, and still had features of both mouse and human cells, limiting its benefits. Eventually scientists figured out how to make drugs using the structures of human antibodies. But they still contained mouse particles. The first of these "chimeric antibodies" was the cancer drug Rituxan launched in 1997. It has transformed how we treat lymphoma by improving survival while reducing treatment side effects.

Scientists "humanized" these antibody drugs still further with the launch of the breast cancer drug Herceptin in 1998. But it wasn't until the approval of the colon cancer drug Vectibix in 2006 that the first "fully human" cancer antibody medicine arrived.

Ipilimumab is part of this new wave of "fully human" antibodies, developed using technology that industry perfected in the late 1990s. Being "fully human," the drug is perfectly matched to bind and disable its target—in this case a protein that can prevent our bodies from attacking the cancer cells.

In contrast to the 30 years of painstaking science that underpins Ipilimumab, the drug Crizotinib is the product of discoveries made just in the last decade. It proves that the time between basic science and its translation into new drugs is increasingly shortened as our tools for developing drugs become more sophisticated.

Crizotinib blocks an aberrant protein called ALK that's critical for the spread of cancer cells. The gene it targets was fully discovered in December 2007. Researchers unveiled a study at ASCO of 82 advanced lung-cancer patients with the protein abnormality. The drug shrank or arrested tumors in more than 90% of them.

Advances that flow from our mapping of the human genome enabled the drug's rapid development. Its value to patients is also harnessed by our ability to read the genes in each person's tumor and see if a patient is susceptible to the medicine.

Like all fragile ecosystems, the critical path for translating basic scientific principles into effective medicines is susceptible to outside forces. Lately, these are policies that shrink the incentives that drive the capital investment needed to underwrite these long and risky endeavors, or growing regulation by the Food and Drug Administration that makes it harder to get treatments to market.

Most ominous, the journey from lab to treatment is at risk from activists' and regulators' growing suspicion of the collaboration between the academic researchers who uncover basic science and the drug industry that is able to design and manufacture medicines. Yet that hand-off from researcher to manufacturer was behind Ipilimumab, Crizotinib and many of our best cancer treatments. Too many policy makers don't fully grasp how dissimilar and specialized these fields really are. Now Congress is endeavoring to investigate scientists who get National Institutes of Health research grants and also collaborate with industry.

The future promises much shorter periods between the uncovering of vital scientific principals and their conversion into useful medicines. Severing the links between the academic researchers that firm up basic science and the industries that craft medicines is the surest way to reverse this trend.

(Nanowerk News) The long, anxious wait for biopsy results could soon be over, thanks to a tissue-imaging technique developed at the University of Illinois.

The research team demonstrated the novel microscopy technique, called nonlinear interferometric vibrational imaging (NIVI), on rat breast-cancer cells and tissues. It produced easy-to-read, color-coded images of tissue, outlining clear tumor boundaries, with more than 99 percent confidence – in less than five minutes.

Led by professor and physician Stephen A. Boppart, who holds appointments in electrical and computer engineering, bioengineering and medicine, the Illinois researchers will publish their findings on the cover of the Dec. 1 issue of the journal Cancer Research.

In addition to taking a day or more for results, current diagnostic methods are subjective, based on visual interpretations of cell shape and structure. A small sample of suspect tissue is taken from a patient, and a stain is added to make certain features of the cells easier to see. A pathologist looks at the sample under a microscope to see if the cells look unusual, often consulting other pathologists to confirm a diagnosis.

"The diagnosis is made based on very subjective interpretation – how the cells are laid out, the structure, the morphology," said Boppart, who is also affiliated with the university's Beckman Institute for Advanced Science and Technology. "This is what we call the gold standard for diagnosis. We want to make the process of medical diagnostics more quantitative and more rapid."

Rather than focus on cell and tissue structure, NIVI assesses and constructs images based on molecular composition. Normal cells have high concentrations of lipids, but cancerous cells produce more protein. By identifying cells with abnormally high protein concentrations, the researchers could accurately differentiate between tumors and healthy tissue – without waiting for stain to set in.

Each type of molecule has a unique vibrational state of energy in its bonds. When the resonance of that vibration is enhanced, it can produce a signal that can be used to identify cells with high concentrations of that molecule. NIVI uses two beams of light to excite molecules in a tissue sample.

"The analogy is like pushing someone on a swing. If you push at the right time point, the person on the swing will go higher and higher. If you don't push at the right point in the swing, the person stops," Boppart said. "If we use the right optical frequencies to excite these vibrational states, we can enhance the resonance and the signal."

One of NIVI's two beams of light acts as a reference, so that combining that beam with the signal produced by the excited sample cancels out background noise and isolates the molecular signal. Statistical analysis of the resulting spectrum produces a color-coded image at each point in the tissue: blue for normal cells, red for cancer.

Another advantage of the NIVI technique is more exact mapping of tumor boundaries, a murky area for many pathologists. The margin of uncertainty in visual diagnosis can be a wide area of tissue as pathologists struggle to discern where a tumor ends and normal tissue begins. The red-blue color coding shows an uncertain boundary zone of about 100 microns – merely a cell or two.

"Sometimes it's very hard to tell visually whether a cell is normal or abnormal," Boppart said. "But molecularly, there are fairly clear signatures."

The researchers are working to improve and broaden the application of their technique. By tuning the frequency of the laser beams, they could test for other types of molecules. They are working to make it faster, for real-time imaging, and exploring new laser sources to make NIVI more compact or even portable. They also are developing new light delivery systems, such as catheters, probes or needles that can test tissue without removing samples.

"As we get better spectral resolution and broader spectral range, we can have more flexibility in identifying different molecules," Boppart said. "Once you get to that point, we think it will have many different applications for cancer diagnostics, for optical biopsies and other types of diagnostics."

ScienceDaily (Feb. 8, 2011) — Much of the devastation of stroke and head trauma is due to damage caused the overproduction of a substance in the brain called glutamate. Preventing this damage has been impossible, until now, as many drugs don't cross the so-called blood-brain barrier, and those that do often don't work as intended. But a method originally devised at the Weizmann Institute of Science may, in the future, offer a way to avert such glutamate-induced harm.

Prof. Vivian I. Teichberg of the Institute's Neurobiology Department first demonstrated a possible way around these problems in 2003. Glutamate -- a short-lived neurotransmitter -- is normally all but absent in brain fluids. After a stroke or injury, however, the glutamate levels in brain fluid become a flood that over-excites the cells in its path and kills them. Instead of attempting to get drugs into the brain, Teichberg had the idea that one might be able to transport glutamate from the brain to the blood using the tiny "pumps," or transporters, on the capillaries that work on differences in glutamate concentration between the two sides. Decreasing glutamate levels in blood would create a stronger impetus to pump the substance out of the brain. He thought that a naturally-occurring enzyme called glutamate-oxaloacetate transaminase (GOT, for short) could "scavenge" blood glutamate, significantly lowering its levels. By 2007, Teichberg and his colleagues had provided clear evidence of the very strong brain neuroprotection that oxolacetate (a chemical similar to GOT) afforded rats exposed to a head trauma.

Two new studies -- conducted by Francisco Campos and others from the lab of Prof. Jose Castillo in the University of Santiago de Compostela, Spain -- now provide a definitive demonstration of Teichberg's results. In the first, the scientists conclusively showed that oxoloacetate injected into rats with stroke-like brain injuries reduces glutamate levels both in the blood and in the affected brain region, while significantly lessening both cell death and the swelling that can accompany stroke. In the second, a team of neurologists in two different hospitals checked the levels of glutamate and GOT in several hundred stroke victims who were admitted to their hospitals. They found that the most significant predictor of the prognosis -- how well they would recover at three months and how much brain damage they would suffer -- was the levels of these two substances. High glutamate levels correlated with a poor outcome, high GOT levels with a better one.

The overall implication of these two papers is that administering GOT might improve a patient's chances of recovering, as well as speeding up the process. In addition to stroke and head trauma, a number of diseases are characterized by an accumulation of glutamate in the brain, including Alzheimer's disease, Parkinson, multiple sclerosis, epilepsy, glaucoma, certain brain tumors and amyotrophic lateral sclerosis, and there is hope that, in the future, treatments to scavenge glutamate could relieve the symptoms and improve the outcomes for a number of neurological problems. Yeda, the technology transfer arm of the Weizmann Institute, holds a patent for this method.

Benefits of Electrical Stimulation Therapy Found With People Paralyzed by Spinal Cord Injury

ScienceDaily (Feb. 18, 2011) — A new treatment approach which uses tiny bursts of electricity to reawaken paralyzed muscles "significantly" reduced disability and improved grasping ability in people with incomplete spinal cord injuries, according to results published February 17.

In a study posted online in the journal Neurorehabilitation and Neural Repair, Toronto researchers report that functional electrical stimulation (FEFirst-of-its-kind study shows benefits of electrical stimulation therapy for people paralyzed by spinal cord injuryS) therapy worked considerably better than conventional occupational therapy alone to increase patients' ability to pick up and hold objects.

FES therapy uses low-intensity electrical pulses generated by a pocket-sized electric stimulator. Unlike permanent FES systems, the one designed by Dr. Popovic and colleagues is for short-term treatment. The therapist uses the stimulator to make muscles move in a patient's limb. The idea is that after many repetitions, the nervous system can 'relearn' the motion and eventually activate the muscles on its own, without the device.

The randomized trial, believed to be the first of its kind, involved 21 rehabilitation inpatients who could not grasp objects or perform many activities of daily living. All received conventional occupational therapy five days per week for eight weeks. However, one group (9 people) also received an hour of stimulation therapy daily, while another group (12 people) had an additional hour of conventional occupational therapy only.

Patients who received only occupational therapy saw a "gentle improvement" in their grasping ability, but the level of improvement achieved with stimulation therapy was at least three times greater using the Spinal Cord Independence Measure, which evaluates degree of disability in patients with spinal cord injury.

Based on their findings, the study's authors recommend that stimulation therapy should be part of the therapeutic process for people with incomplete spinal cord injuries whose hand function is impaired.

Dr. Popovic's team has almost completed a prototype of their stimulator, but need financial support to take it forward. Dr. Popovic thinks the device could be available to hospitals within a year of being funded. One limitation of the study is that the research team could not get all participants to take part in a six-month follow-up assessment. However, six individuals who received FES therapy were assessed six months after the study. All had better hand function after six months than on the day they were discharged from the study.

Dr. Popovic stresses that FES therapy should augment, and not replace, existing occupational therapy. Another study, now underway, will determine whether stimulation therapy can improve grasping ability in people with chronic (long-term) incomplete spinal cord injuries.

"This study proves that by stimulating peripheral nerves and muscles, you can actually 'retrain' the brain," says the study's lead author, Dr. Milos R. Popovic, a Senior Scientist at Toronto Rehab and head of the Rehabilitation Engineering Laboratory. "A few years ago, we did not believe this was possible."

ScienceDaily (Feb. 28, 2011) — A Wayne State University School of Medicine physician-researcher has developed a personalized therapy to treat a wide range of cancers. The treatment is based on a naturally occurring human enzyme that has been genetically modified to fool cancer cells into killing themselves.

The unique concept, patented by Wayne State University, was successfully demonstrated on melanoma cells that are resistant to routine treatments such as chemotherapy or radiotherapy. Melanoma is a perfect model for testing this new therapy because it is considered the most aggressive form of human cancer due to its many defense mechanisms against available treatments. The success of the therapy in killing melanoma suggests a similar outcome in treating other cancers.

Developed by Karli Rosner, M.D., Ph.D., assistant professor and director of Research in the Department of Dermatology, the method uses genetic constructs that contain a genetically modified enzyme -- DNase1 protein -- to seek out and destroy cancer cells. The novel technology was published in the article "Engineering a waste management enzyme to overcome cancer resistance to apoptosis: adding DNase1 to the anti-cancer toolbox" in the Jan. 14 online edition of Cancer Gene Therapy, a Nature Publishing Group journal.

Dr. Rosner modified the genetic code for DNase1, a highly potent DNA-degrading enzyme, and altered its genetic composition by deleting a part of the code, mutating another part and adding an artificial piece of code. Through these changes, the altered DNA program is translated into a modified protein. In contrast to the natural protein, the modified protein will not be eliminated from the cancer cell, will resist deactivation by cell inhibitors and will gain access to the cell's nucleus. "If you imagine the cell's nucleus as a computer and DNA in the nucleus as computer software," Dr. Rosner explained, "then the altered, hacked DNA program corresponds to a computer virus."

"To further understand this anti-cancer technology," he continued, "recollect the plot from the movie, Independence Day. In this movie, a computer virus is introduced into an alien ship to neutralize its defenses and make it vulnerable to external weapons. We do something similar but much better by introducing the altered genetic code of DNase1 into the DNA of cancer cells alien to the healthy body." The cancer cell, unaware of the destructive potential of the modified code, translates it into a protein that evades the cell's defense mechanisms and enters the nucleus. In the nucleus, the protein damages DNA by chopping it into fragments without the need for external weaponry, i.e., other medications. Following damage to DNA, the cell's organelles disintegrate and the cancer cell dies. In this way, Dr. Rosner's technology leads cancer cells into committing suicide because he fools them into generating the protein that will cause their own death.

The beauty of this therapy is that specifically-targeted cancer cells destroy themselves through the physiological mechanism of apoptosis, leaving surrounding healthy cells intact. This mode of cancer cell elimination leaves no residual debris to alert the immune system to kick in, essentially committing "the perfect crime," Dr. Rosner said. This is important because the many side effects of current anti-cancer treatments are attributed to activation of the immune system. The fact that this therapy does not require participation of the patient's immune system to kill cancer cells is a big advantage over other newly developed technologies, such as the cancer vaccine. Those technologies depend on the patient's immune system to destroy cancer. Unfortunately, they are not effective in the presence of a compromised immune system, which is true for many cancer patients. In contrast, Dr. Rosner's therapy will be able to treat even the most severely immuno-compromised patients with the same degree of success as in treating patients with a fully functional immune system.

Patients with the same cancer type vary in their response to identical treatment because the biological characteristics of the same cancer type usually differ between patients. As a result, the medical field strives to develop treatments that can be adjusted to each patient. The structure of Dr. Rosner's technology is flexible in that it contains Lego-like pieces that together form a genetic construct. Each piece can be replaced by one of several other genetic pieces that perform the same task, but differ slightly in their genetics. The multiple options available for each genetic piece will allow the physician to tailor the finalized treatment to each patient based on the unique characteristics of his or her cancer. In this way, the new technology is a "true personalized therapy" he said. The physician will expose a patient's cancer cells obtained by biopsy, to various genetic constructs to identify the version of therapy that kills the patient's cancer with the utmost efficiency.

Of particular importance is the potential for this technology to treat a large variety of tumors, such as prostate, lung and breast cancers. Dr. Rosner likened the therapy to the military's Tomahawk missile platform. The Tomahawk is directed to its target by programming the missile's homing device. Likewise, the destructive genetic construct can be targeted to a particular cancer type by incorporating a genetic piece that specifically identifies the cancer. Multiple genetic homing devices will be at the physician's disposal. The ability to target the therapy specifically to cancer cells will reduce side effects common with today's anti-cancer therapies. Moreover, the ability to target multiple cancers will immensely increase the number of cancer patients who will benefit from the new technology.

The one side effect that Dr. Rosner foresees is the potential for lightening of skin hue at a level that he cannot predict, but that's a tradeoff someone suffering from metastatic cancer and given a limited prognosis may accept in exchange for becoming cancer-free. To date, Dr. Rosner has demonstrated cancer cell kill rates of 70 to 100 percent with his first generation of "gene suicide therapy." To further increase the killing efficiency, he has recently designed a second generation of constructs. In the near future he intends to test the therapy in an animal model, an intermediate step required before moving the treatment into clinical trial.

"Although this has been tested on melanoma cell lines, Dr. Rosner's approach can be tailored to other types of tumors," said Darius Mehregan, M.D., the Hermann Pinkus Chair of the Department of Dermatology. "I think it is important for other researchers in the Wayne State University system to be aware of possibilities to collaborate, and for the pharmaceutical industry to be aware of the economic potential of this novel technology."

This week in California, we began a new and potentially historic effort to end cancer.

On Monday in Los Angeles, with the support of Mayor Antonio Villaraigosa, leading cancer researchers and organizations dedicated to finding a cure, we kicked off our California Cancer Research Act campaign.

The California Cancer Research Act will make California stronger by saving lives, stopping kids from smoking, and investing more money than any other state in the country to find solutions for cancer. The initiative, which would raise $780 million annually through a $1 per pack tax on cigarettes, would provide an ongoing source of funds to allow California's leading medical researchers to pursue new ways to detect, treat, prevent and cure cancer and other tobacco-related illnesses.

The money raised from tobacco sales would be administered by scientists, researchers and universities -- not by politicians.

We are honored to be co-chairing this campaign on behalf of all of the incredible people dedicated to ending cancer. The American Cancer Society. The American Lung Association. The American Heart Association. Stand Up to Cancer. We can go on and on.

We hate cancer. We have both been personally touched by the disease, as has everyone else in America, either directly or indirectly. It is estimated that more than 500,000 Americans will die of cancer this year. More than 1,500 people a day. Cancer is the leading cause of death worldwide and the second highest cause of death in the U.S., accounting for nearly one of every four lives lost.

The successful passage of the California Cancer Research Act would help reduce these numbers -- and make California stronger along the way. A report by the state

We are excited to see that California is already mobilizing to make history in the fight against cancer.

Institutions including schools in the UC system, Stanford, City of Hope and world-renowned Cedars-Sinai would benefit from millions of dollars in annual funding for cancer research -- and that is what is motivating people to get involved in supporting this measure.

We all know that as California goes, so goes the rest of the nation and that is what makes this initiative so important. If the people of California are successful in setting a new record for cancer research funding, it will only be a matter of time before the entire country makes fighting cancer a top priority.

[comment - if such campaigns target behaviour, then they should consider they would gain better results with prevention. I see that doing both could produce better results overall, neither will end cancer]

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